On the role of glucose-dependent insulintropic polypeptide in postprandial metabolism in humans

Abstract

(GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of triglycerides (TAG), and free fatty acids (FFA) in humans. First, 20 healthy males received intravenous infusion of GIP (0.8 pmol · kg Ϫ1 · min Ϫ1 ) or saline for 300 min during and after a fixed meal (protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males received intravenous infusions of Intralipid, glucose, or Intralipid plus glucose, with and without GIP (1.5 pmol · kg Ϫ1 · min Ϫ1 ) for 300 min (protocol 2). In protocol 1, GIP did not have any effect on GE, EI, EE, removal of TAG, or FFA and did not influence the subjective feeling of hunger, satiety, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen in the plasma TAG on Intralipid ϩ GIP/saline and Intralipid ϩ glucose ϩ GIP/saline days. FFA concentrations were lower on Intralipid ϩ glucose ϩ GIP/saline days (P Ͻ 0.05) compared with Intralipid ϩ GIP/saline days and on Intralipid ϩ GIP day (P Ͻ 0.004) compared with Intralipid ϩ saline day. Insulin increased on all GIP days compared with saline days (P Ͻ 0.05). In conclusion, while confirming its insulinotropic effects, these data suggest that GIP does not affect GE, appetite, energy intake, EE, or the clearance rate of the applied TAG formulation in humans. However, both insulin and GIP lower post-Intralipid FFA concentration, GIP probably via stimulation of insulin secretion, increasing FFA reesterification. gastric emptying; energy intake; energy expenditure; appetite; insulin OBESITY IS A CONSEQUENCE of an imbalance between food intake and energy expenditure, and several lines of evidence suggest a role for glucose-dependent insulinotropic polypeptide (GIP) in the development of obesity. GIP is a hormone secreted from endocrine K cells located in the proximal part of the small intestine in connection with food intake (18,31,38), and it stimulates insulin secretion in a glucose-dependent manner (2,11,36). Early observations of elevated plasma GIP concentrations in type 2 diabetic patients (8,12,14,43) and obese diabetic ob/ob mice (21) drew attention to a possible role of GIP in fat metabolism. This is supported by studies (3) demonstrating that high-fat feeding induced K-cell hyperplasia and enhanced GIP gene expression. Furthermore, it has been shown that GIP is released by lipids and that 24-h GIP profiles parallel the plasma concentration of triglycerides (TAG; Ref. 15), leading to speculation that GIP might play a part in the postprandial regulation of TAG. In dogs, infusion of GIP significantly lowered the rise in plasma TAG after infusion of chylomicrons (45), while in rats exogenous and endogenous GIP lowered the plasma TAG response to a fat load (13). In adipose tissue, GIP has been shown to stimulate glucose transport and increase fatty acid synthesis (24), enhance lipoprotein...

Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase

“…Our results are also in agreement with a recent study in human subjects in which authors used a prolonged high insulin high glucose clamp technique with plasma glucose and insulin concentrations similar to those found after ingestion of a carbohydraterich meal (59). They found that during the high insulin high glucose clamp experiment in combination with GIP, glucose uptake in adipose increased significantly compared with the high insulin high glucose clamp experiment without GIP.…”

Transgenic Rescue of Adipocyte Glucose-dependent Insulinotropic Polypeptide Receptor Expression Restores High Fat Diet-induced Body Weight Gain

“…Other studies have measured weight of excised fat depots finding smaller inguinal, epididymal, and perirenal fat pads in the GIPr Ϫ/Ϫ mice (21), whereas GIP antagonism in DIO mice has been reported to result in a reduction in subcutaneous WAT but not epididymal and perirenal fat (46); the latter study is very much in line with what we observe in our cohort. Similar results could be seen in humans where GIP did not affect acute whole body lipid metabolism (54), but during a hyperinsulinemic-hyperglycemic clamp, GIP could be seen to increase lipid and glucose uptake in a subcutaneous abdominal fat pad (55). Accordingly, GIP may differentially modulate adiposity depending on type of WAT.…”

Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery

“…Again, it might be assumed that a maximal effect of endogenously secreted GIP on ␤-cell function was already obtained on the control days. Accordingly, Asmar et al (1) reported no further effect on insulin secretion when additional GIP was infused during a meal that by itself caused a large endogenous GIP response. However, the peaks of total and intact GIP in the present study amounted to only about one-third of the responses during meal tests with DPP-4 inhibition in nonoperated individuals, which raises the possibility that an attenuated GIP response after RYGB surgery explains the present findings (17,59).…”